Drug Delivery at the Immunological Synapse

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We have given names to nearly all the different protein molecules that mediate communication between human cells. Now, the audacious goal of contemporary cell biology is to understand how the billion proteins in an average cell allow them to move, multiply, create a brain or defend us against viruses and bacteria. Imaging where and when proteins interact with each other has a major role to play at this frontier. Recent imaging of just a few types of proteins has already led to important new concepts in how immune cells communicate with each other and how they recognize signs of disease. Images of immune cells contacting other cells have revealed temporary membrane structures, often called immune synapses, similar to the synapses that nerve cells make with one another for communication. It has been postulated that one function for such an immune synapse is to assemble a 'gasket' that to some extent isolates the synaptic cleft from the bulk extracellular environment. However, the precise extent as to which the synapse acts as a gasket has not been studied. This fundamental knowledge can have a major importance for the design of novel drugs, because understanding to what extent and how the immune synapse is shielded from the bulk extracellular environment could, in the longer term, facilitate the rational design of drugs that penetrate the immune synapse to work more effectively, e.g. for blocking proteins secreted across the synapse. It may also be useful to note that to realize the proposed experiments we will exploit new imaging technologies which will be of broad interest across several biological research fields. Patents may be sought upon development of specific applications. In addition to the specific hypotheses to be studied here, the application of high-resolution microscopy to study immune cell interactions is also to some extent explorative and hypothesis-forming; this is still a very young field and more surprises are surely in store.